Super-antigens are distinguished from conventional antigens by the fact that they stimulate large numbers of T cells based predominantly on the expression of specific T cell antigen receptor Vbeta elements. Bacterial super-antigens are toxins responsible for a variety of diseases in man and animal including toxic shock and food poisoning. Moreover, bacterial super-antigens have been implicated in a number of autoimmune diseases such as Reiter's syndrome and ankylosing spondylitis. Retroviral super- antigens have a major effect on the T cell repertoire because they mediate the clonal elimination of large numbers of T cells to maintain self-tolerance potentially resulting in diminished T cell responsiveness to foreign antigen. The long term objective of the proposed study is to characterize the interaction between T cells, major histocompatibility complex (MHC) molecules and super-antigens at a cellular and molecular level. The experimental approach takes advantage of a well characterized system in which murine Vbeta17+ T cells interact with a super-antigen (vSAG-9) controlled by an endogenous mouse mammary tumor virus integrant, Mtv-9. This system is of particular interest because this interaction has been shown to be critically dependent on the haplotype of the MHC molecule. First, the contribution of non-Vbeta elements to the recognition of vSAG- 9 will be determined by characterizing the T cell receptors of two panels of Vbeta17+ hybridomas which specifically recognize vSAG-9 in the context of either H-2(k) or H-2(d). Second, these studies will be extended to determine whether the MHC haplotype specificity is a characteristic of other super-antigen/Vbeta systems. Third, the processing of vSAG-9 will be investigated by analyzing the ability of various cell types to transcribe, process and present this super-antigen to T cells.